On the evening of September 29, after State Senator George Yarbrough withdrew the State Highway Police, a riot broke out. Whites opposing integration had been gathering at the campus. Despite the Kennedy administration's reluctance to use force, it ordered the nationalized Mississippi National Guard and federal troops to the campus. In the violent clashes which followed, two men were killed by gunshot wounds, and the white mob burned cars, pelted federal marshals with rocks, bricks and small arms fire, and damaged university property.

The next day on October 1, 1962, after troops took control, Meredith became the first African-American student to enroll at the University of Mississippi. Meredith's admission is regarded as a pivotal moment in the history of civil rights in the United States. He persisted through harassment and extreme isolation to graduate on August 18, 1963, with a degree in political science.

Many students harassed Meredith during his two semesters on campus, but others accepted him. According to first-person accounts, students living in Meredith's dorm bounced basketballs on the floor just above his room through all hours of the night. Other students ostracized him: when Meredith walked into the cafeteria for meals, the students eating would turn their backs. If Meredith sat at a table with other students, all of whom were white, the students would immediately get up and go to another table.